BACKGROUND: Little is known about whether tolerability and adherence to treatment can be influenced by weather and temperature conditions. The objective of this study was to assess monthly and seasonal adherence to and safety of sc IFN-β1a (Rebif®, Merck) in relapsing-remitting multiple sclerosis (RRMS) patients using the RebiSmart® electronic autoinjector.METHODS: A multicentre, prospective observational study in Greece in adult RRMS patients with EDSS < 6, under Rebif®/RebiSmart® treatment for ≤6 weeks before enrollment. The primary endpoint was monthly, seasonal and annual adherence over 12 months (defined in text). Secondary endpoints included number of relapses, disability, adverse events.RESULTS: Sixty four patients enrolled and 47 completed all study visits (Per Protocol Set - PPS). Mean annual adherence was 97.93% ± 5.704 with no significant monthly or seasonal variations. Mean relapses in the pre- and post- treatment 12-months were 1.1 ± 0.47 and 0.2 ± 0.54 (p < 0.0001, PPS). 10 patients (22%) showed 3-month disability progression, 19 (40%) stabilization and 18 (38%) improvement. EDSS was not correlated to pre- (r = 0.024, p = 0.87) or post-treatment relapses (r = 0.022, p = 0.88).CONCLUSION: High adherence with no significant seasonal or weather variation was observed over 12 months. While the efficacy on relapses was consistent with published studies, we could not identify a relationship between relapses and disability.TRIAL REGISTRATION: Greek registry of non-interventional clinical trials ID: 200136 , date of registration: February 18th, 2013.